FG Syndrome Type 1

Synonyms of FG Syndrome Type 1

FGS1

Opitz-Kaveggia syndrome

Subdivisions of FG Syndrome Type 1

No subdivisions found

General Discussion

FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and downslanting eyes.
FGS1 is an X-linked genetic disorder typically caused by a recurrent abnormality (mutation) in the MED12 gene. The spectrum of disorders caused by mutations in this gene is still being defined. Some individuals previously diagnosed with FG syndrome do not have a MED12 gene mutation and, therefore, probably have a different reason for intellectual disability.

Signs & Symptoms

FG syndrome type 1 (FGS1) is an X-linked genetic disorder that is characterized by poor muscle tone (hypotonia), intellectual disability, constipation and or anal anomalies and complete or partial absence of the part of the brain that connects the two hemispheres of the brain (corpus callosum). Other features of the disorder are small and simple ears, tall and prominent forehead, wide and flat thumbs and great toes and downslanting eyes. Additional features may include a large head (macrocephaly), widely spaced eyes (ocular hypertelorism) and upswept frontal hair. Seizures and congenital heart defects have also been reported.

Individuals with FGS1 often have characteristic behaviors that can include hyperactivity, friendliness and attention seeking.

Causes

FGS1 is typically caused by a recurrent abnormality (mutation) in the MED12 gene on the X chromosome located at Xq13. The MED12 gene is responsible for production of the MED12 (TRAP230) protein that is involved in the regulation of transcription.

FGS1 is an X-linked genetic disorder. X-linked genetic disorders are conditions caused by an abnormal gene on the X chromosome and occur mostly in males. Females that have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms because females have two X chromosomes and one is inactivated so that the genes on that chromosome are nonfunctioning. It is usually the X chromosome with the abnormal gene that is inactivated. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a disease gene he will develop the disease. Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

Males with X-linked disorders pass the disease gene to all of their daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male offspring.

Affected Populations

The prevalence of FGS1 is unknown. The spectrum of disorders caused by mutations in this gene is still being defined. Some individuals previously diagnosed with FG syndrome do not have a MED12 gene mutation and, therefore, probably have a different reason for intellectual disability.

Related Disorders

Symptoms of the following disorders can be similar to those of FGS1 syndrome. Comparisons may be useful for a differential diagnosis:

Lujan syndrome is an X-linked genetic disorder in the spectrum of disorders caused by mutations in the MED12 gene. This condition is characterized by intellectual disability, hypotonia, large head, tall and thin body, long and thin face and high and narrow palate. Additional features that may be present include small jaw, long hands with hyperextensible digits, abnormalities of the corpus callosum and nasal speech.

X-linked Opitz G/BBB syndrome is an X-linked genetic condition characterized by multiple birth defects including facial anomalies, abnormalities involving the trachea, larynx and esophagus and abnormalities of the genitourinary system. Cleft lip and palate are also common. Developmental delay and intellectual disability occur in about half of those affected. Heart defects, imperforate anus and defects in the midline of the brain can also occur.

Diagnosis

FGS1 syndrome is suspected based on the presence of physical characteristics. Molecular genetic testing for the MED12 gene is available and is the only way to confirm the diagnosis.

Standard Therapies

Treatment

The symptoms of FGS1 syndrome are treated individually. This usually involves care by a team of providers including a pediatrician, neurologist, cardiologist, surgeon, gastroenterologist and psychologist. Early intervention with physical, occupational and speech therapy should be initiated as soon as possible.

Genetic counseling is recommended for affected individuals and their family members.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Years Published

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